The Vascular Effects of Endothelin Receptor Antagonism in Systemic Vasculitis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Study 1 - forearm blood flow
研究概览
简要总结
Patients with vasculitis commonly develop cardiovascular disease. The reasons for this are not clear and is not adequately treated with current drugs. It is thus understand the reasons why patients with vasculitis develop cardiovascular disease in order to develop new drugs to reduced this risk.
Endothelin is a chemical produced by blood vessels that contributes to the development of hypertension and cardiovascular disease Higher than normal levels of endothelin are seen in patients with vasculitis but how this contributes to cardiovascular disease in patients with vasculitis is not clear. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') the investigators can hopefully reduce the risk of cardiovascular disease in patients with vasculitis. The purpose of the study is to ascertain if endothelin receptor antagonists improve blood vessel function in patients with vasculitis.
详细描述
Vasculitis patients and healthy controls matched for age, sex will be enrolled into the study. Patients will attend for 4 study days >1 week apart, whereas controls will attend for single day. Circulating Mφ and other immune cells will be confirmed using FACS prior each study.
Study 1 Both patients and control will attend for visit 1: assessment of vascular function using forearm plethysmography as part of case control study.
Vasculitis patients will then attend for visits 2, 3 & 4 as part of randomised three way crossover study (randomised & infusions given in a double-blind method): comparison of the effects of selective ETA receptor antagonism (BQ123; 1000nmol/min for 15min iv), mixed ETA/B antagonism (BQ123/788; 1000 nmol/min & 300 nmol/min for 15 min), and placebo on systemic haemodynamics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female
- •Age 18 years and over
- •Body mass index ≤35
- •Normal serum albumin
排除标准
- •Subject with diabetes or current smoking or chronic kidney disease (eGFR <60ml/min)
- •Subject with pre-existing cardiovascular disease
- •Subject is below the age of legal consent, or is mentally or legally incapacitated
- •History of multiple and/or severe allergic reactions to drugs (including study drugs)
- •The subject has donated blood (450 ml) within the last 4 weeks
- •Past or present drug or alcohol abuse including intravenous drug abuse at any time
- •Participation in another clinical trial within 1 month
- •Considered to be at high risk of HIV or hepatitis B
- •Women of child-bearing potential (only women who are post-menopausal or surgically-sterilised will be included in the study)
研究组 & 干预措施
Placebo
Saline placebo
干预措施: Placebo (Drug)
BQ123
Intravenous infusion of BQ123 1000nmol/min for 15min
干预措施: BQ123 (Drug)
BQ123/788
Intravenous infusion of BQ123 1000nmol/min and BQ788 300nmol/min
干预措施: BQ123/788 (Drug)
结局指标
主要结局
Study 1 - forearm blood flow
时间窗: 20mins
Response to endothelium-dependent vasodilators
Study 2 - pulse wave velocity
时间窗: 4 hours
Response of participants to ET antagonism
次要结局
- Study 1 - tPA release(20min)
- Study 1 - baseline pulse wave velocity(Baseline)
- Study 2 - tPA release(4 hours)